This research effort is aimed at study of antinuclear antibody in systemic rheumatic diseases such as systemic lupus erythematosus, Sjogren's syndrome, rheumatoid arthritis, scleroderma, dermatomyositis and mixed connective tissue disease. We are interested in determining the specificities of circulating antinuclear antibodies, i.e., the nature of the nuclear antigens with which these autoantibodies react. The antigens will be characterized according to whether they are nucleic acids, histones or nonhistones nuclear proteins. The role of autoantibodies in pathogenesis of tissue injury will be investigated. Specifically, we are interested in the importance of these autoantibodies in generalized vasculitis, in glomerulonephritis and in cerebral arteritis. The more basic aspects of this research will involve the use of the autoantibodies as biological reagents to isolate the respective nuclear antigens. The nuclear antigens will be obtained in amounts sufficient for chemical analysis and immunochemical characterization.